乳腺癌组织中HIF-1α的表达水平及其与肿瘤血管生成相关性研究

Investigation of HIF-1αexpression and angiogenesis in breast cancer tissue

目的:探讨缺氧诱导因子1α(hypoxia inducible factor 1α,HIF-1α)在乳腺正常组织、不典型增生、原位癌、浸润性癌组织中的表达水平,分析其与浸润性乳腺癌临床病理指标及肿瘤血管生成之间的关系。方法:收集20例正常乳腺组织、23例不典型增生、34例原位癌、80例浸润性乳腺癌组织标本,用免疫组化SP法检测各组中HIF-1α的表达,分析其在浸润性乳腺癌中的表达与肿瘤大小、腋窝淋巴结受累情况、TNM分期、组织学分级、激素受体等临床病理指标之间的关系。并用CD34标记肿瘤新生血管,分析HIF-1α表达对肿瘤血管生成的影响。结果:HIF-1α在正常乳腺组织中未见阳性表达,在乳腺不典型增生组织、原位癌组织、浸润性癌组织中表达阳性率分别为8.7%(2/23)、47.1%(16/34)及73.8%(59/80),表达率依次增高,乳腺原位癌组织与不典型增生组织之间、乳腺浸润癌组织与原位癌组织之间差异具有统计学意义(P<0.01)。在浸润性乳腺癌中,HIF-1α的表达在不同肿瘤直径、组织学分级及淋巴结转移分组中差异具有统计学意义(P均<0.05)。浸润性导管癌HIF-1α阳性组MVD值(11.74±4.398)明显高于HIF-1α表达阴性组(9.093±2.856),差异有统计学意义(P<0.05)。HIF-1α表达与MVD值呈正相关性(r=0.633,P<0.05)。结论:HIF-1α在浸润性乳腺癌组织中表达水平升高,其表达上调与乳腺癌新生血管生成密切相关。

Objective:To study the expression of HIF-1αin normal tissue of breast,atypical hyperplasia,ductal carcinoma in situ and invasive carcinoma,and analyze the associations with pathological features and angiogenesis in human breast cancer.Methods:Expressions of HIF-1αin 20 cases of normal breast tissue,23 cases of atypical hyperplasia,34 cases of DCIS(ductal carcinoma in situ)and 80 cases of invasive carcinoma were determined by IHC(immunohistochemistry)technique respectively.The expression of HIF-1αin 80 cases of invasive breast cancer was analyzed against the clinical and pathology features such as tumor diameter,lymph node status and so on.The blood vessels were labeled with CD34.The effect of HIF-1αexpression on tumor angiogenesis was analyzed.Results:There was no expression of HIF-1αin normal breast tissue.The positive rates of HIF-1αexpression in atypical hyperplasia,carcinoma in situ and invasive cancer were 8.7%(2/23),47.1%(16/34)and 73.8%(59/80).The differences between atypical hyperplasia and carcinoma in situ,carcinoma in situ and invasive cancer were statistically significant(P<0.01).In invasive breast cancer,the expressions of HIF-1αin different tumor diameter,pathology grades and lymph node metastasis groups were statistically significant(P<0.05).The MVD value of HIF-1αpositive group(11.74±4.398)was significantly higher than that of HIF-1αnegative group(9.093±2.856),and the difference was statistically significant(P<0.05).There was a positive correlation between the expression of HIF-1αand MVD(r=0.633,P<0.05).Conclusion:HIF-1αis highly expressed in invasive breast cancer,and the upregulation of HIF-1αis closely related to angiogenesis of breast cancer.